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An experiment carried out with 3 g. of 1,a-benzylidene glycerol, similarly treated with dry hydrogen chloride but without any preliminary heating and allowed to stand for one month a t room temperature, yielded 0.45g. of l,3-benzylidene glycerol.
Summary 1. The preparation, isolation, quantitative separation and interconversion of the isomeric 1,2- and 1,3-benzylidene glycerols are described. 2 . The corresponding methyl ethers have been prepared and their physical constants determined. 3. The remarkably labile character of the oxygen ring is shown by the ease of partial transformation of either of the acetals into the corresponding isomer a t a low temperature under the influence of traces of gaseous hydrochloric acid. The bearing of this on polysaccharide investigations is pointed out. 4. Glycerol P-methyl ether has been isolated for the first time in a pure state. I t is apparently the first pure P-derivative of glycerol to be reported in the literature. MONTREAL, CANADA ___I__
[COMMUNICATION FROM THE DEPARTMENT OF INDUSTRIAL A N D CELLULOSE CHEMISTRY, MCGILLUNIVERSITY]
STUDIES ON THE REACTIONS RELATING TO CARBOHYDRATES AND POLYSACCHARIDES. XVI. SEPARATION AND IDENTIFICATION OF THE ISOMERIC ETHYLIDENE GLYCEROLS'
s.
B Y HAROLD HILL,*ALLANc. HILL)AND HAROLD HIBBERT' RECEIVED APRIL 14, 1928
PUBLISHED Aucusr 4 , 1928
The importance of the cyclic acetal and ketal glycerols has long attracted the interest of investigators in the field of carbohydrate chemistry. Such workers as Tollens,j Fischer,6 Karrer,' Irvine,8 and more recently This work was presented by Mr. Allan C. Hill to the Graduate Department, McGill University, in ,4pril, 1937, in partial fulfilment of the requirements for the degree of Master of Science. Research Fellow, Canadian Pulp and Paper Association. Research Chemist attached to Pulp and Paper Division, Forest Products Laboratories of Canada. This paper represents the second of a forthcoming series of publications carried out under the joint auspices of the Canadian Pulp and Paper Association, the Pulp and Paper Division of the Forest Products Laboratories of Canada and the Department of Industrial and Cellulose Chemistry, McGill University. The authors wish to express their keen appreciation of the generous facilities placed at their disposal by the three cooperating agencies. Schulz and Tollens, Ann., 289, 29 (1896). 6 Fischer, Ber., 27, 1536 (1897). Karrer, Helv. Chim. Acta, 4, 728 (1921). Irvine, Macdonald and Soutar, J . Chem. Sac., 107,337 (1915).
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Hibbert and his pupils9 have studied or used this class of compounds in their efforts to explain, by analogy, certain features of the chemical behavior of the more complex polysaccharides. It is remarkable, therefore, that up to the present time the molecular structure of one of the simplest glycerol acetals, namely, ethylidene glycerol, has remained undetermined, its formula being given as either, or both, of the two possible isomeric forms CHz-O>CHCH3 CH-0
I
CH2OH (A)
yH2-’\
or CHOH ,CHCH3
I
CHz-0 (B)
L.
Schulz and toll en^,^ working with the lower homolog, methyfidene glycerol, indicated the existence of both of the corresponding isomeric forms since, under different experimental conditions, they were able to obtain products which, in one case, yielded a benzoate as a crystalline product, in the other as an oil. The isomers were not identified, however, and the method used in their preparation left some doubt as to their existence as different chemical individual^.^" With respect to the structure of ethylidene glycerol, however, there has been no evidence brought forward as to which of the two forms, A or B, should be assigned as its molecular constitution. This is due in large part to the extreme ease of hydrolysis of this product and the consequent difficulty of obtaining any derivative not involving rupture of the acetal ring. Ethylidene glycerol was first prepared by Harnitzky and Menschutkinelo and later, in much purer form, by Nef,” the formula being given as either A or B. Recent work12 has shown that in benzaldehyde condensations with glycerol a “partition” occurs, both the five and the six membered cyclic acetals being formed simultaneously. In view of these results, as well as those from earlier experiments in this field,g i t was concluded that ethylidene glycerol would also prove to be a mixture of the two ring systems (A) and (B). The present investigation deals with the separation and identification of these isomers, and of several of their derivatives. The isomeric ethylidene glycerols are obtained as a mixture in either of the two recognized methods of p r e p a r a t i ~ n . ~The crude product in both Hill and Hibbert, THIS JOURNAL, 45, 3121 (1923). Neal Carter has recently succeeded in isolating and identifying the two pure methylidene glycerols and their corresponding benzoates. An account of this work is to be published in the immediate future. (H. H.) Harnitzky and Menschutkine, Ann., 136, 126 (1865). l 1 Nef, Ann., 335, 216 (1904). Hill, Khelen and Hibbert, THIS JOURKAL, 50, 2235 (1928).
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cases boils a t 176-187' (760 mm.), the rise in temperature during distillation, even with a fractionating column, being very gradual. Operating under reduced pressure, however, i t is possible, by several fractionations, to obtain two distinct products, Fraction I, b. p. 86-88' (21 mm.), and Fraction 11, b. p. 101-103.5" (20 mm.), neither of which, however, can be considered as a pure material. The acetylene method of preparation yielded the sharpest boiling low fraction, while that from the paraldehyde method gave the most definite high boiling product. From this observation it would appear that the partition between the two isomeric forms of ethplidene glycerol may vary considerably, according to the method and conditions of preparation. The fractions from either method have the same percentage composition and each, upon hydrolysis with dilute phosphoric acid, yields the same theoretical amount of acetaldehyde. Differences in the densities and refractive indices, however, further indicate the presence of isomers. Many unsuccessful attempts were then made, using the low boiling fraction from the acetylene method and the high boiling from the paraldehyde process (as representing the purest samples), to isolate an acglated product, and this was finally achieved by the use of benzoyl chloride in dry pyridine solution. This reagent causes no hydrolysis of the acetal ring and readily yields two well defined glycerol-acetal-benzoates, that from the low boiling fraction being crystalline (m. p. 86') and that from the high boiling product an oil, b. p. 163 (11 mm.). The isolation of these benzoates in a pure state proved to be the key to this research, especially since a fortunate difference in solubility in ligroin permitted of an almost quantitative separation. Employing the mixture of isomers obtained by the acetylene method, benzoylating the product and separating the mixed benzoates by the use of cold ligroin, it was possible to isolate the isomeric benzoates, the ratio of the amounts of the crystalline to the liquid form being 1:1.8. This ratio may be regarded as an approximately accurate value of the extent of the partition between the low and high boiling ethylidene glycerols, respectively, as prepared by this method. Applying the same procedure to the mixture of ethylidene glycerols obtained from the reaction of paraldehyde with glycerol, the relative amounts of the low and high boiling isomers were found to be 1:4. Two conclusions may be drawn from these partitions. 1. The formation of the high boiling isomer-later shown to have the five membered cyclic configuration (A)-is definitely favored over that of the six membered derivative (B). 2. The partition ratio is a variable one, the relative amounts of each isomer formed depending on experimental conditions such as temperature, concentration of acid, etc. There is no reason to suppose that the actual mechanism of ring closure is any different in the
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preparation from acetylene than from paraldehyde. Furthermore, i t is to be expected, as found in the preceding paper12 (Part XV) on the isomeric benzylidene glycerols that under standard conditions, there will always exist a final equilibrium mixture which should be the same irrespective of whether this is approached from the side of the five or from that of the six membered acetal. Structural Identification of the Isomers.-Since the isomeric ethylidene glycerol benzoates may thus be separated and isolated in a pure condition, these derivatives were used as the starting point to determine the structure of the original acetals. It was found possible t o hydrolyze off the benzoyl group, leaving the acetal ring intact. In this way, starting with the pure benzoates, two isomeric ethylidene glycerols were obtained for the first time, as pure individual compounds. The structures of these acetals were determined essentially as in the case of the benzylidene glycerols, namely, by the methylation-hydrolysis method developed by Irvine and co-workers. Silver oxide and methyl iodide was used as the methylating agent, since Haworth’s methyl sulfate method proved unsatisfactory. Each of the two ethylidene glycerols yielded an isomeric ethylidene glycerol methyl ether which, in turn, on hydrolysis, gave an isomeric glycerol monomethyl ether. The low boiling ethylidene glycerol (purified through its crystalline benzoate) gave only glycerol @-methylether, identical with tbat isolated for the first time from 1,3-benzylidene glycerol, while the higher boiling ethylidene glycerol (from its liquid benzoate) yielded only the glycerol amethyl ether. In the latter case, while the a-ether was the main product, there was also a small amount of the @-derivativepresent. This was due to its imperfect removal in the purification of the benzoate, since it is admittedly impossible to separate completely all of the solid from the liquid benzoate, but this fact does not affect the conclusions drawn as to the structure of the products. It is considered proved, therefore, that in the preparation of ethylidene glycerol, a partition occurs between the five and six membered rings, and also that the low boiling acetal has definitely the 1,3-configuration (B) while the higher boiling isomer has the alternate 1,2-structure (A). Comparative Properties of the Isomers.-Four pairs of isomeric glycerol derivatives, namely, 1,2- and 1,3-ethylidene glycerols, their corresponding benzoates, their methyl ethers and a- and @-glycerolmethyl ethers, have now been synthesized and i t is believed that their properties offer an interesting physico-chemical study. For purposes of comparison some properties and physical constants are collected in the following table. Certain generalizations may be drawn from the results in Table I. I n all
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H. S. HILL, A. C. HILI, AND HAROLD HIBBERT
TABLE I PHYSICAL CONSTANTS OF COMPOUNDS B. p.,
